ArticleJHLT open2026
Macitentan and phosphodiesterase-5 inhibitor alone or in combination in newly diagnosed pulmonary arterial hypertension: a pooled analysis.
Article in JHLT open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
introductionUpfront combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i) is guideline-recommended for low- or intermediate-risk pulmonary arterial hypertension (PAH). This study compared time to all-cause mortality for macitentan+PDE5i combination and each monotherapy.
methodsLong-term patient-level data (planned follow-up ≥1 year) were pooled from four clinical trials and three observational registries. All-cause mortality data were available from adults with incident PAH initiated on macitentan 10 mg or PDE5i monotherapy, or macitentan+PDE5i. Propensity-score (PS) methods balanced key demographic and disease characteristics across cohorts. Hazard ratios (HRs) were computed from a Cox-regression model that included PS-calculated weights. Weighted Kaplan-Meier estimates with 95% confidence intervals (CI) were computed 6-monthly.
results2201 patients were included: 754 received macitentan+PDE5i (421 tadalafil, 324 sildenafil, 9 other), 654 macitentan, and 793 PDE5i (301 tadalafil, 490 sildenafil, 2 other). After weighting, characteristics were similar across cohorts. Upfront macitentan+PDE5i was associated with a 39% risk reduction of all-cause mortality versus PDE5i (HR 0.61 [95% CI 0.46-0.82]) and 32% versus macitentan (HR 0.68 [95% CI 0.37-0.95]). Reduction in all-cause mortality was 49% for macitentan+tadalafil vs tadalafil (HR 0.51 [95% CI 0.30-0.85]), 43% for macitentan+tadalafil vs macitentan (HR 0.57 [95% CI 0.37-0.88]), 31% for macitentan+sildenafil vs sildenafil (HR 0.69 [95% CI 0.45-1.0]) and 26% for macitentan+sildenafil vs macitentan (HR 0.74 [95% CI 0.46-1.17]).
conclusionThis large, pooled analysis suggests an observed statistical association indicating a potential survival benefit for early macitentan+PDE5i versus either monotherapy in newly diagnosed PAH.
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